Fermented Gracilaria lemaneiformis polysaccharides alleviate food allergy by regulating Treg cells and gut microbiota.

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Occurrence and seasonal variation of Perkinsus sp. Infection in wild mollusk populations from coastal waters of Qingdao, northern China.

Perkinsosis has been recognized as one of the major threats to natural and farmed bivalve populations, many of which are of commercial as well as environmental significance. Three Perkinsus species have been identified in China, and the Manila clam (Ruditapes philippinarum) was the most frequently infected species in northern China. Although the occurrence and seasonal variation of Perkinsus spp. have previously been examined, the pathological characteristics of these infections in wild Manila clams and sympatric species in China have seldom been reported. In the present study, the prevalence and intensity of Perkinsus infection in wild populations of Manila clams and 10 sympatric species from three sites were investigated by Ray's fluid thioglycolate medium (RFTM) assay seasonally across a single year. Perkinsus infection was only identified in Manila clams, with a high prevalence (274/284 = 96.48 %) and low intensity (89.8 % with a Mackin value ≤ 2, suggesting generally low-intensity infections) throughout the year. Heavily infected clams were mainly identified in Tianheng in January, which displayed no macroscopic signs of disease. An overview of the whole visceral mass section showed that the trophozoites mostly aggregated in gills and connective tissue of the digestive tract, to a lesser extent in the mantle and foot, and even less frequently in adductor muscle and connective tissues of the gonad. PCR and ITS-5.8S rRNA sequencing of 93 representative RFTM-positive samples revealed a 99.69 to 100 % DNA sequence identity to Perkinsus olseni. Unexpectedly, significantly higher infection intensities were usually identified in January and April when the Condition Index (CI) was relatively high. We propose that factors associated with the anthropogenic harvesting pressure and irregular disturbances should be responsible for the uncommon seasonal infection dynamics of perkinsosis observed in the present study.

The Probiotic Bacillus hwajinpoensis Colonizes the Digestive System of Crassostrea gigas Larvae and Protects Them from Vibrio alginolyticus Infection.

The Pacific oyster Crassostrea gigas is one of the most important cultured marine species around the world. Production of Pacific oysters in China has depended primarily on hatchery produced seeds since 2016, with the successful introduction and development of triploid oysters. However, the seed supply of Pacific oysters is threatened by recurring mass mortality events in recent years. Vibriosis is the most commonly encountered disease associated with intensive oyster culture in hatcheries and nurseries. Vibrio alginolyticus and Bacillus hwajinpoensis were the two strains with pathogenic and probiotic effects, respectively, identified during the Pacific oyster larvae production. To monitor their colonization process in Pacific oyster larvae, green fluorescent protein (GFP) and red fluorescent protein (RFP) were labeled to the pathogenic V. alginolyticus and the probiotic B. hwajinpoensis stain, respectively. The pathogenic and probiotic effects of the two strains during the colonization process were then assessed. Stabile expression of GFP and RFP were observed in corresponding stains, and the capabilities of growth, biofilm formation and in vitro adhesion of GFP- and RFP- tagged stains were not significantly different from those of the wild-type strains. Usage of probiotics of 105 CFU/mL significantly inhibited the growth of pathogenic V. alginolyticus and reduced the mortality of D-sharped larvae. Both the pathogenic and probiotic strains employed a similar route to enter and colonize the oyster larvae, which indicates that competing with pathogens for binding and spreading sites were one of the mechanisms of B. hwajinpoensis to provide the probiotic effects to oyster larvae. In summary, employment of fluorescence-tagged pathogenic and probiotic strains simultaneously provides us with an excellent bioassay model to investigate the potential mechanisms of probiotics.

MHC class II regulation of CD8+ T cell tolerance and implications in autoimmunity and cancer immunotherapy.

Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.

Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation.

Cellular immunity mediated by CD8+ T cells plays an indispensable role in bacterial and viral clearance and cancers. However, persistent antigen stimulation of CD8+ T cells leads to an exhausted or dysfunctional cellular state characterized by the loss of effector function and high expression of inhibitory receptors during chronic viral infection and in tumors. Numerous studies have shown that glycogen synthase kinase 3 (GSK3) controls the function and development of immune cells, but whether GSK3 affects CD8+ T cells is not clearly elucidated. Here, we demonstrate that mice with deletion of Gsk3α and Gsk3ß in activated CD8+ T cells (DKO) exhibited decreased CTL differentiation and effector function during acute and chronic viral infection. In addition, DKO mice failed to control tumor growth due to the upregulated expression of inhibitory receptors and augmented T-cell exhaustion in tumor-infiltrating CD8+ T cells. Strikingly, anti-PD-1 immunotherapy substantially restored tumor rejection in DKO mice. Mechanistically, GSK3 regulates T-cell exhaustion by suppressing TCR-induced nuclear import of NFAT, thereby in turn dampening NFAT-mediated exhaustion-related gene expression, including TOX/TOX2 and PD-1. Thus, we uncovered the molecular mechanisms underlying GSK3 regulation of CTL differentiation and T-cell exhaustion in anti-tumor immune responses.

Androgen Receptor Transcriptionally Inhibits Programmed Death Ligand-1 Expression and Influences Immune Escape in Bladder Cancer.

In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.

Rehabilitation of knee injury by chinese boxing / Reabilitação em lesão de joelho pelo boxe chinês / Rehabilitación de lesión de rodilla mediante el boxeo chino

ABSTRACT Introduction: Chinese boxing is a highly combative sport and injuries are inevitable. Rehabilitation of knee joint injuries can not only save the athlete's professional career but also improve their prevention ability. Objective: Study the situation of knee joint injuries in Chinese boxing and explore the strategies of sports rehabilitation. Methods: This experiment lasted 8 weeks. The knee joint activity and daily exercise ability of the control and experimental groups were tested. Results: In the experimental group, the knee joint extension range was increased to - 1.61° (± 2.228), the knee joint flexion range was increased to 97.14° (± 6.430), the walking ability score was increased to 32.25 (± 5.751) points, and the stair climbing and descending ability score was increased to 35.12 (± 8.764) points. The control group's scores were also optimized, but the range of optimization was smaller than that of the experimental group. Conclusion: Compared with traditional physical therapy and massage, sports rehabilitation training has a more significant effect on improving the range of motion and prevention ability on athletes' knee joints and should be promoted. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O boxe chinês é um esporte altamente combativo e suas lesões são inevitáveis. A reabilitação de lesões nas articulações do joelho pode não apenas salvar a carreira profissional do atleta como também melhorar a sua capacidade de prevenção. Objetivo: Estudar a situação das lesões nas articulações do joelho pelo boxe chinês e explorar as estratégias de reabilitação esportiva. Métodos: Esta experiência teve duração de 8 semanas. A atividade articular do joelho e a capacidade de exercício diário dos grupos controle e experimental foram testadas. Resultados: No grupo experimental, o alcance da extensão da articulação do joelho foi aumentado para - 1,61° (± 2,228), o alcance da flexão da articulação do joelho foi aumentado para 97,14° (± 6,430), a pontuação da capacidade de caminhar foi aumentada para 32,25 (± 5,751) pontos, e a pontuação da capacidade de subir e descer escadas foi aumentada para 35,12 (± 8,764) pontos. Os índices do grupo de controle também foram otimizados, mas a faixa de otimização foi menor do que a do grupo experimental. Conclusão: Em comparação com a fisioterapia e massagem tradicionais, o treinamento de reabilitação esportiva tem um efeito mais significativo na melhoria da amplitude de movimento e na capacidade de prevenção sobre as articulações dos joelhos dos atletas, devendo ser promovido. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El boxeo chino es un deporte altamente combativo y sus lesiones son inevitables. La rehabilitación de las lesiones de la articulación de la rodilla no sólo puede salvar la carrera profesional del deportista, sino también mejorar su capacidad de prevención. Objetivo: Estudiar la situación de las lesiones de la articulación de la rodilla por el boxeo chino y explorar las estrategias de rehabilitación deportiva. Métodos: Este experimento duró 8 semanas. Se comprobó la actividad de la articulación de la rodilla y la capacidad de ejercicio diario de los grupos de control y experimental. Resultados: En el grupo experimental, el rango de extensión de la articulación de la rodilla aumentó a - 1,61° (± 2,228), el rango de flexión de la articulación de la rodilla aumentó a 97,14° (± 6,430), la puntuación de la capacidad de caminar aumentó a 32,25 (± 5,751) puntos, y la puntuación de la capacidad de subir y bajar escaleras aumentó a 35,12 (± 8,764) puntos. Las puntuaciones del grupo de control también se optimizaron, pero el rango de optimización fue menor que el del grupo experimental. Conclusión: En comparación con la fisioterapia tradicional y el masaje, el entrenamiento de rehabilitación deportiva tiene un efecto más significativo en la mejora de la amplitud de movimiento y la capacidad de prevención en las articulaciones de la rodilla de los atletas y debería promoverse. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Heart rate monitoring in special training for boxers / Monitoramento de frequência cardíaca em treino especial para boxeadores / Monitorización de frecuencia cardíaca en entrenamiento especial para boxeadores

ABSTRACT Introduction Chinese boxing is an aggressive, competitive, and combative sport. During its performance, good physical fitness and a stable heart rate can determine the athletes' sports performance. Objective Study special physical training methods of Chinese boxing athletes by monitoring their heart rates. Methods The implementation period of the experiment totaled eight weeks, performed three times a week. The control group did not get any specific physical training while the experimental group received special physical training, properly protocoled. Their indices were measured before, during, and after the experiment, with classification and data analysis by Excel and SPSS software. Results The fitness data of the experimental group were significantly improved, with the heart rate more stable, corroborating the effectiveness of the special training. Conclusion The use of special physical training can optimize and better adjust the pre-existing protocol according to the athletes' real competition needs, improving the specialized physical fitness and the athletes' competitive level. It also helps stabilize the heart rate, helping athletes get better results in combat. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMO Introdução O boxe chinês é um esporte agressivo, competitivo e combativo. Durante a sua execução, a boa forma física e a frequência cardíaca estável podem determinar o desempenho esportivo dos atletas. Objetivo Estudar métodos especiais de treinamento físico dos atletas de boxe chinês monitorando suas frequências cardíacas. Métodos O período de implementação do experimento totalizou oito semanas, executado três vezes por semana. O grupo de controle não obteve nenhum treinamento físico específico enquanto o grupo experimental recebeu um treinamento físico especial, devidamente protocolado. Seus índices foram mensurados antes, durante e depois do experimento, com classificação e análise de dados pelos programas Excel e SPSS. Resultados Os dados de aptidão física do grupo experimental foram significativamente aprimorados, com frequência cardíaca foi mais estável, corroborando a eficácia do treinamento especial. Conclusão O uso de treino físico especial pode otimizar e ajustar melhor o protocolo pré-existente, de acordo com as necessidades reais de competição dos atletas, melhorando a aptidão física especializada e o nível competitivo dos atletas. Também auxilia na estabilização da frequência cardíaca, ajudando os atletas a obterem melhores resultados em combate. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El boxeo chino es un deporte agresivo, competitivo y combativo. Durante su ejecución, el buen estado físico y el ritmo cardíaco estable pueden determinar el rendimiento deportivo de los atletas. Objetivo Estudiar los métodos de entrenamiento físico especial de los atletas de boxeo chinos mediante la monitorización de sus frecuencias cardíacas. Métodos El periodo de aplicación del experimento fue de ocho semanas, realizado tres veces por semana. El grupo de control no obtuvo ningún entrenamiento físico específico, mientras que el grupo experimental recibió un entrenamiento físico especial, debidamente protocolizado. Se midieron sus índices antes, durante y después del experimento, con clasificación y análisis de datos mediante los programas Excel y SPSS. Resultados Los datos de aptitud física del grupo experimental mejoraron significativamente, con una frecuencia cardíaca más estable, lo que corrobora la eficacia del entrenamiento especial. Conclusión El uso del entrenamiento físico especial puede optimizar y ajustar mejor el protocolo preexistente, de acuerdo con las necesidades reales de competición de los atletas, mejorando la aptitud física especializada y el nivel competitivo de los atletas. También ayuda a estabilizar el ritmo cardíaco, ayudando a los atletas a obtener mejores resultados en el combate. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Study on physical training in the lipid metabolism regulation of obese adolescents / Estudo sobre treinamento físico na regulação do metabolismo lipídico em adolescentes obesos / Estudio sobre el entrenamiento físico en la regulación del metabolismo lipídico en adolescentes obesos

ABSTRACT Introduction In proportion to the development of the economy, the problem of obesity among adolescents is also increasing. This abnormal lipid metabolism index can influence other physical diseases besides harming the social development of youth. Objective Investigate physical training and the regulation of lipid metabolism in adolescents, improving the metabolic index of obese youth. Methods 80 obese adolescents with equal numbers of both genders were randomly assigned into experimental and control groups. The experimental group received daily 80-min sports training (aerobics, walking, badminton, swimming, and other sports with low intensity and long duration) six times a week for one month, without distinction of exercise intensity or frequency for gender. A comparison method was performed between the groups before and after the intervention with indicators including body weight, BMI, fluid ratio, water measurement, waist, hip, skinfold thickness, FBG, CT, Tg, HDL - C, and LDL - C, among others. Results Physical training can effectively improve adolescents' body shape. Blood indices and other indicators except for HDL-C positively correlate with this body shape. Physical training substantially improved lipid metabolism in obese adolescents. Conclusion The exercise regimen of this experiment proved to be simple and manageable, offering adolescents a healthier physical and more confidence in their daily study, life, and social interaction, but also reducing several diseases caused by obesity. Due to the ease of replication, the sample size can be expanded to universal conclusions, making it feasible to popularize. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Proporcionalmente ao desenvolvimento da economia, aumenta também o problema da obesidade entre os adolescentes. Esse índice anormal no metabolismo lipídico pode influenciar outras doenças físicas além de prejudicar o desenvolvimento social na juventude. Objetivo Investigar o treinamento físico e a regulação do metabolismo lipídico em adolescentes, melhorando o índice metabólico dos jovens obesos. Métodos 80 adolescentes obesos com número igual de ambos os sexos foram distribuídos aleatoriamente em grupos controlados de experimento e controle. O grupo experimental recebeu treinamentos esportivos diários de 80 minutos (aeróbica, caminhada, badminton, natação e outros esportes com baixa intensidade e longa duração), seis vezes por semana durante um mês, sem distinção de intensidade ou frequência dos exercícios para os sexos. Foi realizado o método de comparação entre os grupos, antes e após a intervenção, com indicadores incluindo peso corporal, IMC, taxa de líquidos, medição de água, cintura, quadril, espessura de dobras cutâneas, FBG, CT, Tg, HDL - C, LDL - C entre outros. Resultados O treinamento físico pode melhorar efetivamente a forma corporal dos adolescentes. Índices sanguíneos e outros indicadores com exceção do HDL-C estão positivamente correlacionados com essa forma corporal. O treinamento físico melhorou substancialmente o metabolismo lipídico de adolescentes obesos. Conclusão O esquema de exercícios deste experimento demonstrou-se simples e viável, oferecendo aos adolescentes um físico mais saudável e mais confiança no processo de estudo diário, vida e interação social, mas também reduzir diversas doenças causadas pela obesidade. Devido a facilidade de replicação, o número de amostrar pode ser expandido para conclusões universais, viabilizando a sua popularização. Nível de evidência II; Estudos terapêuticos - investigação dos desfechos do tratamento.

RESUMEN Introducción Proporcionalmente al desarrollo de la economía, el problema de la obesidad entre los adolescentes también aumenta. Este índice anormal en el metabolismo lipídico puede influir en otras enfermedades físicas además de perjudicar el desarrollo social en la juventud. Objetivo Investigar el entrenamiento físico y la regulación del metabolismo lipídico en adolescentes, mejorando el índice metabólico de los jóvenes obesos. Métodos 80 adolescentes obesos con igual número de ambos sexos fueron distribuidos aleatoriamente en los grupos de experimento y de control. El grupo experimental recibió 80 minutos diarios de entrenamiento deportivo (aeróbic, marcha, bádminton, natación y otros deportes de baja intensidad y larga duración), seis veces a la semana durante un mes, sin distinción de intensidad o frecuencia de los ejercicios para los sexos. Se realizó un método de comparación entre los grupos, antes y después de la intervención, con indicadores que incluían el peso corporal, el IMC, la tasa de líquidos, la medición del agua, la cintura, la cadera, el grosor de los pliegues cutáneos, FBG, CT, Tg, HDL - C, LDL - C, entre otros. Resultados El entrenamiento físico puede mejorar eficazmente la forma corporal de los adolescentes. Los índices sanguíneos y otros indicadores, excepto el HDL-C, están positivamente correlacionados con esta forma corporal. El entrenamiento físico mejoró sustancialmente el metabolismo de los lípidos en los adolescentes obesos. Conclusión El esquema de ejercicios de este experimento demostró ser simple y factible, ofreciendo a los adolescentes un físico más saludable y más confianza en el proceso de estudio diario, la vida y la interacción social, pero también reduciendo varias enfermedades causadas por la obesidad. Debido a la facilidad de replicación, el tamaño de la muestra puede ampliarse para obtener conclusiones universales, lo que permite su popularización. Nivel de evidencia II; Estudios terapêuticos - investigación de los resultados del tratamiento.

Thermal Remediation of Soil Contaminated with Polycyclic Aromatic Hydrocarbons: Pollutant Removal Process and Influence on Soil Functionality.

Thermal remediation has been widely used for the removal of polycyclic aromatic hydrocarbon (PAH) from contaminated soil. The method has a high removal rate for semi-volatile organic pollutants; however, soil functionality is affected by the method because of the alteration of the soil properties. In this study, experimental soil was impregnated with phenanthrene (Phe), pyrene (Pyr), and benzo(a)pyrene (BaP); after natural air-dry aging, the thermal remediation experiment was carried out, using a tube-furnace and thermal gravimetry-Fourier transform infrared (TG-FTIR) equipment. More than 84% of the Phe and Pyr were lost in the aging stage, whereas the BaP was stable with 41% retention in the soil. After the thermal treatment, the desorption and decomposition of the pollutants and organic matter led to the removal of the PAHs; about 1% of the PAHs remained in the soil treated at 400 °C. The presence of the PAHs can promote the thermal reaction by slightly reducing the reaction activation energy by ~7-16%. The thermal remediation had a significant influence on the physical properties of the soil and destroyed the bioavailability by reducing the organic matter content. Therefore, a comprehensive consideration of effective PAH removal while preserving soil functionality may require a low temperature (100 °C) method for thermal remediation.

A Novel Salt-Bridge Electroflocculation Technology for Harvesting Microalgae.

Microalgae biomass, as a promising alternative feedstock, can be refined into biodiesel, pharmaceutical, and food productions. However, the harvesting process for quality biomass still remains a main bottleneck due to its high energy demand. In this study, a novel technique integrating alkali-induced flocculation and electrolysis, named salt-bridge electroflocculation (SBEF) with non-sacrificial carbon electrodes is developed to promote recovery efficiency and cost savings. The results show that the energy consumption decreased to 1.50 Wh/g biomass with a high harvesting efficiency of 90.4% under 300 mA in 45 min. The mean particle size of algae flocs increased 3.85-fold from 2.75 to 10.59 µm, which was convenient to the follow-up processing. Another major advantage of this method is that the salt-bridge firmly prevented cells being destroyed by the anode's oxidation and did not bring any external contaminants to algal biomass and flocculated medium, which conquered the technical defects in electro-flocculation. The proposed SBEF technology could be used as a low cost process for efficient microalgae harvest with high quality biomass.

Sulfate oligosaccharide of Gracilaria lemaneiformis modulates type 1 immunity by restraining T cell activation.

Seaweeds are important "blue food" and some seaweeds have been demonstrated that have the immunoregulation activities and benefit for human health. However, which immune cell subsets are targeted and how immune processes are regulated by those seaweeds remain poorly understood. Here we identified sulfated oligosaccharide of Gracilaria lemaneiformis (GLSO) inhibits IFNγ production by T cells in ovalbumin (OVA) immunized mice and in vitro activation system of OVA-specific CD4+ T cells. Furthermore, GLSO predominantly targets T cells but not dendritic cells, and regulates the late stage of expression of T cell activation and differentiation markers. Mechanistically, results of transcriptomic and proteome analysis indicate that GLSO inhibits mTOR activity, glycolysis, cell cycle and DNA replication. Thus, GLSO has an immunomodulatory function in Th1 immune responses by restraining T cell activation. Our study unravels the anti-inflammatory mechanism of GLSO and provides a new insight for industrial development of seaweeds as health food.

A prophylactic effect of aluminium-based adjuvants against respiratory viruses via priming local innate immunity.

Infection caused by respiratory viruses can lead to a severe respiratory disease and even death. Vaccination is the most effective way to prevent the disease, but it cannot be quickly applied when facing an emerging infectious disease. Here, we demonstrated that immunization with an aluminium-zinc hybrid particulate adjuvant (FH-001) alone, bearing great resemblance in morphology with commonly used aluminium-based adjuvants in vaccines, could quickly induce mice to generate a broadly protective immune response to resist the lethal challenge of influenza B viruses. Furthermore, a multi-omics-based analysis revealed that the alveolar macrophage and type I interferon pathway, rather than adaptive immunity and type II interferon pathway, were essential for the observed prophylactic effect of FH-001. More importantly, a similar protective effect was observed against influenza A virus strain A/Shanghai/02/2013(H7N9), A/California/04/2009(H1N1) and respiratory syncytial virus. Therefore, we introduced here a new and promising strategy that can be quickly applied during the outbreak of emerging respiratory viruses.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Glycogen synthase kinase 3 drives thymocyte egress by suppressing ß-catenin activation of Akt.

Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell­specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, ß-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P1 expression, thereby preventing emigration of thymocytes. A cytoplasmic membrane-localized ß-catenin excluded from the nucleus promoted Akt activation, suggesting a new function of ß-catenin independent of its role as a transcriptional activator. Furthermore, genetic ablation of ß-catenin, retroviral expression of a dominant negative Akt mutant, and transgenic expression of a constitutively active Foxo1 restored emigration of GSK3-deficient thymocytes. Our findings establish an essential role for GSK3 in thymocyte egress and reveal a previously unidentified signaling function of ß-catenin in the cytoplasm.

Bioengineered Nanocage from HBc Protein for Combination Cancer Immunotherapy.

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Naïve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.

Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application.

OBJECTIVES: Complement activation product C5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning. This study is to explore the efficiency of anti-C5a-based intervention on systemic inflammatory responses induced by paraquat poisoning. DESIGN: Study of cynomolgus macaque model and plasma from paraquat-poisoning patients. SETTING: Laboratory investigation. SUBJECTS: Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16). INTERVENTIONS: The neutralizing antihuman C5a antibody (IFX-1) was administered to investigate the new treatment strategy for paraquat-induced systemic inflammatory responses in cynomolgus macaque model. In addition, C5a activation in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade role of anti-C5a antibody in activation of inflammatory cells. MEASUREMENTS AND MAIN RESULTS: Dysregulated complement activation and the subsequent cytokine storm were found in patients with acute lung injury and in a primate model of paraquat poisoning. Targeted inhibition of C5a by IFX-1 led to marked alleviation of systemic inflammatory responses and multiple organ damage in the primate model. In addition, blockade of C5a activity in plasma from patients completely inhibited activation of CD11b on blood granulocytes from normal donors, suggesting that IFX-1 may alleviate the excessive activation of inflammatory responses and have clinical utility for patients with acute lung injury. CONCLUSIONS: Anti-C5a antibodies such as IFX-1 may be used as effective therapeutics for treatment of those suffering from systemic inflammatory responses induced by chemical poisoning like paraquat.

A Mathematical Model of Neutral Lipid Content in terms of Initial Nitrogen Concentration and Validation in Coelastrum sp. HA-1 and Application in Chlorella sorokiniana.

Microalgae are considered to be a potential major biomass feedstock for biofuel due to their high lipid content. However, no correlation equations as a function of initial nitrogen concentration for lipid accumulation have been developed for simplicity to predict lipid production and optimize the lipid production process. In this study, a lipid accumulation model was developed with simple parameters based on the assumption protein synthesis shift to lipid synthesis by a linear function of nitrogen quota. The model predictions fitted well for the growth, lipid content, and nitrogen consumption of Coelastrum sp. HA-1 under various initial nitrogen concentrations. Then the model was applied successfully in Chlorella sorokiniana to predict the lipid content with different light intensities. The quantitative relationship between initial nitrogen concentrations and the final lipid content with sensitivity analysis of the model were also discussed. Based on the model results, the conversion efficiency from protein synthesis to lipid synthesis is higher and higher in microalgae metabolism process as nitrogen decreases; however, the carbohydrate composition content remains basically unchanged neither in HA-1 nor in C. sorokiniana.